PETASINFREIE POLAR ONES PETASITESEXTRAKTFRAKTIONEN AND THEIR USE FOR PAIN TREATMENT
(19)AUSTRALIAN PATENT OFFICE (54) Title USE OF COMPOSITIONS CONTAINING PETASITES FOR TREATING DISEASES (51)6 International Patent Classification(s) A61K 035/78 A61P 021/02 (21) Application No: 2003233964 (22) Application Date: 2003.04.11 (87) WIPONo: WO03/088985 (30) Priority Data (31) Number (32) Date 102 17 939.5 2002.04.22 (33) Country DE (43) Publication Date : 2003.11.03 (43) Publication Journal Date : 2003.12.11 (71) Applicant(s) WEBER AND WEBER GMBH AND CO. KG (72) Inventor(s) RITTINGHAUSEN, Reiner (H) Application NoAU2003233964 A1(19)AUSTRALIAN PATENT OFFICE (54) Title USE OF COMPOSITIONS CONTAINING PETASITES FOR TREATING DISEASES (51)6 International Patent Classification(s) A61K 035/78 A61P 021/02 (21) Application No: 2003233964 (22) Application Date: 2003.04.11 (87) WIPONo: WO03/088985 (30) Priority Data (31) Number (32) Date 102 17 939.5 2002.04.22 (33) Country DE (43) Publication Date : 2003.11.03 (43) Publication Journal Date : 2003.12.11 (71) Applicant(s) WEBER AND WEBER GMBH AND CO. KG (72) Inventor(s) RITTINGHAUSEN, Reiner The use of a Petasites extract (and/or its fraction(s)) (A) for: (1) the production of a specific cyclooxygenase-2 (COX-2) inhibitor; (2) treatment and/or prophylaxis of diseases treatable by specific COX-2 inhibition; and/or (3) production of a spasmolytic and/or analgesic medicament. Independent claims are included for: (1) a Petasites extract (and/or its fraction(s)) (A') which contains not more than 30 (preferably less than 0.001) wt. % petasine (I) (based on the solvent-free extract or extract fraction); (2) a specific COX-2 inhibitor based on (A) (in (I)-containing, (I)-depleted or (I)-free form); and (3) a composition based on (A) (in (I)-containing, (I)-depleted or (I)-free form), where (A) is a polar or apolar extract or is enriched with a polar and/or apolar extract. - ACTIVITY : Analgesic; antiarthritic; osteopathic; antirheumatic; cytostatic; antiulcer; antiinflammatory; thrombolytic; cardiant; vasotropic; antianginal; cerebroprotective; neuroprotective; hypotensive; antimigraine; antiasthmatic; antiallergic; dermatological; nootropic; tuberculostatic; antipsoriatic; gynecological; tranquilizer; hypnotic; antidepressant; Gastrointestinal-Gen.; Cardiovascular-Gen.; Respiratory-Gen.; Uropathic. - MECHANISM OF ACTION : COX-2 inhibitor. Polar petasites extract fraction(s) that are petasin-free or have a very small petasin content, whereas the petasites extraction fraction(s) have a Rf value (TLC, silica gel 60, eluent toluene / ethyl acetate in the ratio of 93 : 7) in the range of 0 to 0.21. Petasites extract fraction(s) according to claim 1, characterized in that the petasites extract fraction(s) is obtained from a plants, parts of plants, and/or plant cells. Petasites extract fraction(s) according to claim 1 or 2, characterized in that the petasites extract fraction(s) is obtained from a transformed plant, parts of plants, and/or plant cells, preferably with agrobacterium rhizogenes transformed cultures thereof, in particular transformed hairy root cultures. Petasites extract fraction(s) according to any one of the preceding claims, characterized in that the petasites extract fraction(s) is obtained from plants and/or parts of plants of petasites hybridus, petasites albus, petasites japonicus, petasites paradoxus, petasites formosanus, petasites kablikianus, petasites tricholobus, petasites niveus, petasites amplus, petasites georgicus, petasites fragrans and/or petasites spurius, whereas the subterraneous plant parts are used for the preparation of the extract. Petasites extract fraction(s) according to any one of the preceding claims, characterized in that the petasites extract fraction(s) having between ≥ 0 to ≤ 5 ppm pyrrolizidine alkaloid, preferably ≤ 1 ppm pyrrolizidine alkaloid, especially preferred no pyrrolizidine alkaloid. Composition comprising a petasites extract fraction(s) according to any one of the preceding claims, characterized in that the composition additionally comprise at least one
- antiphlogistic, analgetic, fever reducing agent;- extracts of chamomilla recutita, rhizoma curcumae longae, rhizoma curcumae xanthorrhizae, curcumae xanthorrhiza, cortex salicis, salicis purpurea, salicis daphenoides and/or tanacetum parthenium;- trace elements, preferably salts of chromium, iron, iodine, copper, cobalt, magnesium, manganese, selenium and/or zinc;- secretolytic, secretomotoric, preferably extracts of the licorice root, thyme and/or peppermint oil;- bronchospasmolytic, preferably extracts of ivy leaves, calendula and/or viola;- vitamin, preferably vitamin A, B, C, D, E and/or K; and/or- antioxidant, preferably lycopene, lutein, zeaxanthin, bioflavonoids, grape seed extract. Composition according to claim 6, characterized in that at least one substance is added to the composition, that increase the resorption in the gastrointestinal tract, whereas the substance that increases the resorption comprises preferably an emulsifier, such as sodium alkyl sulfate , alkyl sulfonate, alkyl carboxylate, alkyl alcoholate, preferably having an alkyl chain length of C12 - C18; polyethyleneglycol fatty alcohol ether; ester as well as ester of polyethyleneglycol with higher fatty acids, fatty alcohols and/or polyethyleneglycolstearate; especially preferred cetylstearylalcohol and/or glycerinepolyethyleneglycolricinoleate. Composition according to claim 6 or 7, characterized in that at least one substance is added to the composition, that decelerates the resorption in the gastrointestinal tract, whereas the substance that decelerates the resorption is preferably selected from the group of paraffins, preferably is a paraffin that is solid at room temperature, especially preferred is a hard paraffin. Composition according to claims 6 to 8, characterized in that at least one taste masking substance is added to the composition, whereas the taste masking substance preferably comprises essential oils, essences, aromatic waters, oil sugars, fruit flavours, aromatic drug extracts, artificial flavours, sugars, polyols having sweetening force, neutral tasting thickening agents, cyclodextrins and/or mixtures thereof. Composition according to claims 6 to 9, characterized in that the composition is present in liquid, gel-type, solid and/or liposomal form. Composition according to claims 6 to 10, characterized in that the composition is a spray, an aerosol, a foam, an inhalant, a powder, a tablet, a capsule, a soft gelatine capsule, a chewable tablet, a salve, a cream, a gel, a suppository or a solution suitable for injection. Composition according to claims 6 to 11, characterized in that the composition is a tablet, a capsule or a chewable tablet, that is formed of micro capsules. Composition according to claims 6 to 12, characterized in that the solid orally administerable pharmaceutical forms are provided with a gastric juice resistant coating. Composition according to claims 6 to 13, characterized in that the administerable daily dose having from between 5 - 600 mg petasites extract fraction(s), preferably from between 10 - 500 mg, mostly preferred 250 mg, based on the total weight of the solvent-free petasites extract fraction(s). Use auf at least one petasites extract fraction(s) according to any one of the claims 1 to 5 and/or of a composition according to any one of the claims 6 to 14 for the production of a pharmaceutically effective composition for the treatment of pains.